concanavalin-a and Cataract

To advance therapy for the treatment of concurrent uveitis and post-cataract surgical inflammation; we evaluated pharmacokinetics and pharmacodynamics of Bioerodible Dexamethasone Implant (BDI) containing 0.3 mg of dexamethasone (DXM) in Concanavalin A (Con A) induced uveitis followed by phacoemulsification in New Zealand White (NZW) rabbits.. The BDI was implanted in the inferior fornix of the capsular bag after intravitreal injection of Con A and ensuing phacoemulsification in NZW rabbits; standard-of-care topical 0.1% dexamethasone drops served as control. DXM was quantified by liquid chromatography-tandem mass spectrometry and pharmacokinetics of DXM in disease vs. healthy eyes was compared. All eyes were assessed clinically using slit lamp biomicroscopy and Draize scoring scale. Retinal thickness and histological analyses were performed to evaluate retinal edema, inflammation and implant biocompatibility respectively.. In Con A-induced inflammatory uveitic cataract model the BDI controlled anterior and posterior segment inflammation as well as retinal thickening more effectively than topical drops. The exposure (AUC0-t) of DXM with BDI is superior in all ocular tissues, while topical drops did not achieve therapeutic posterior segment levels and did not control inflammation nor prevent retinal edema and architectural disruption.. Our results demonstrate the superiority of the BDI in suppressing Con A-induced inflammation and retinal edema in NZW rabbits and highlight the need for sustained bidirectional delivery of potent anti-inflammatory agents for 5 to 6 weeks to optimize clinical outcomes.

Topics: Absorbable Implants; Animals; Anti-Inflammatory Agents; Cataract; Concanavalin A; Dexamethasone; Disease Models, Animal; Drug Delivery Systems; Edema; Female; Inflammation; Ophthalmic Solutions; Rabbits; Retina

Ocular spectroscopy, which is the use of the eye to monitor optically the concentration of metabolites in the body, has been successfully applied to monitor aqueous humor glucose concentration. In the United States, 1.7 million intraocular lenses are currently implanted yearly. Because patients with diabetes are more likely to develop cataracts at an earlier age, a relatively high proportion of the patients receiving intraocular lenses have diabetes. Last year, 110,000 patients with diabetes received intraocular lens implants of various materials. We have successfully polymerized a fluorescent complex within a hydrogel intraocular lens that responds well to glucose concentration.

Topics: Animals; Aqueous Humor; Cataract; Cataract Extraction; Concanavalin A; Dextrans; Diabetes Complications; Fluorescein-5-isothiocyanate; Fluorescence; Fluorescent Dyes; Glucose; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Lens Implantation, Intraocular; Lens, Crystalline; Polyethylene Glycols; Polymers; Rabbits; Rhodamines; Spectrometry, Fluorescence

To evaluate the effect of Concanavalin A (Con A) on cataract formation in New Zealand Albino rabbits. Uveitis is a chronic inflammatory condition of the eye involving the anterior and/or posterior segments. It may be acute or chronic and is associated with the development of posterior subscapular cataract over time. Con A is a nonspecific inflammatory agent and mitogen for T cells and some B cells. Used extensively in immunogenic studies Con A has been shown to induce uveitis after intravitreal injection in New Zealand Albino rabbits.. In two separate studies, Con A was injected intracamerally or intravitreally into one eye of 12 New Zealand Albino rabbits and an equal volume of balanced salt solution was injected into the opposite eye as a control. In a third study, the effect of topical steroids after intravitreal injection of Con A was evaluated. In all studies, anterior and posterior inflammation and the development of cataract was monitored by slit lamp biomicroscopy and photography. Cataract formation was also studied histopathologically.. Initially, all eyes treated with Con A demonstrated moderate anterior chamber inflammation while eyes treated with balanced salt solution showed no inflammation. Three months after treatment, posterior subcapsular cataracts were present in all rabbit eyes treated with intravitreal Con A. In the third study, topical steroid treatment of Con A-induced inflammation significantly reduced anterior chamber inflammation but had no effect on vitreous humor and posterior subcapsular cataract formation.. This experimental model was the first to demonstrate the development of posterior subcapsular cataracts after Con-A induced inflammation. The cataract was clinically and histologically similar to human posterior subscapular cataracts.

Topics: Administration, Topical; Animals; Anterior Chamber; Cataract; Concanavalin A; Disease Models, Animal; Female; Injections; Lens Capsule, Crystalline; Lens, Crystalline; Prednisone; Rabbits; Uveitis, Anterior; Uveitis, Posterior; Vitreous Body

Topics: Aged; Animals; Cataract; Cattle; Concanavalin A; Glycoproteins; Humans; Lens, Crystalline; Rabbits